Patent GB-911815-A (GB)
Title: Steroid compounds and preparation thereof
IPC: C07J1/00
Filed: 1959-03-13
Abstract: The invention comprises steroid compounds of the general formula <FORM:0911815/IV (b)/1> wherein R represents hydrogen or an alkyl radical containing up to 6 carbon atoms, R11 represents an alkyl, alkenyl, or alkynyl radical containing up to 6 carbon atoms, or an acetyl, a ketalised acetyl, a ketalised hydroxyacetyl, a 1,2-dihydroxyethyl or a 1-hydroxyethyl radical, X represents H2, (H)(OH) or O, Y and Y1 represent hydrogen or the methyl radical at least one being a methyl radical, Z represents hydrogen or the hydroxy radical, Z being restricted to hydroxy when R11 represents the alkyl, alkenyl or alkynyl radical, or a carboxylic acid ester of the said steroid, said steroid nucleus, if desired, having a double bond in the 4(5)-position or double bonds in the 4(5)- and 6(7)-positions and, if desired, having halogen atom preferably fluorine, at the 9-position or lower alkyl groups at the 4- or 6-positions, excluding the case where the nucleus is saturated and has the 5a -configuration, R represents hydrogen, and Y and Y1 each represent a methyl radical, R11 is the lower alkyl radical and Z represents the hydroxy radical, no additional nuclear substituents being present; and also excluding the case where a double bond is present in the 4(5)-position, R represents hydrogen, Y represents hydrogen, Y1 represents the methyl radical and R1 represents hydrogen or the alkyl radical; and salts of said steroids; and the preparation of steroids of the above general formula by condensing a compound of the general formula <FORM:0911815/IV (b)/2> wherein Y, Y1, R11 and Z have the above significance, with a compound of the formula RCOOR11, wherein R has the above significance and R111 represents an alkyl radical or an alkanoyl radical when R is an alkyl radical, in the presence of a strong alkali metal base such as an alkali metal lower alkoxide amide or hydride, under anhydrous conditions whereafter, if desired, converting the salt obtained to the free hydroxymethylene compound by means of an acid and, if desired, reacting an acidic product obtained with a basic substance to obtain a salt such as a salt derived from an alkali metal or diethylamine.  The hydroxymethylene products may exist in any of the tautomeric forms as follows:- <FORM:0911815/IV (b)/3> wherein R has the above significance and Q represents the residue of the steroid. Allopregnane-3,20-dione 20-ethylene glycol ketal is prepared by reacting allopregnan-3b -ol-20-one with ethylene glycol and oxidising the resulting allopregnan-3b -ol-20-one 20-ethylene glycol ketal.  6a ,17a  - Dimethylandrostan - 17b -ol-3-one is prepared by treating the corresponding 4-androstene with lithium and ammonia.  6a  - Methyl-17a -propynyl-4-androsten-17b -ol-3-one is prepared by reacting 5-androsten-3b -ol-17-one and propynyl magnesium bromide to form 17a  - propynyl-5-androstene-3b ,17b -diol, acetylating this compound to form the corresponding 3-acetate, treating the 3-acetate with peracetic acid to form 5a ,6a -epoxy-17a -propynyl-androstane-3b ,17b -diol 3-acetate, reacting the 5a ,6a -epoxy compound with methyl magnesium iodide to form 6b -methyl-17a -propynylandrostane - 3b ,5a ,17b -triol, oxidising this compound with chromic oxide to form 6b -methyl-17a -propynyl-androstane-5a ,17b -diol-3-one, and treating this compound with methanolic aqueous potassium hydroxide. Therapeutic compositions having endocrinological or anabolic activity contain as the active ingredient steroid compounds of the first general formula defined above.  The compositions may be in the form of an aqueous suspension, a solution in a suitable oil or oil in water emulsion for parenteral administration, or may be mixed with an excipient to form tablets for oral administration.